Exercise associated myopathies (Proceedings)

Exertional rhabdomyolysis is muscle necrosis precipitated by exercise or exertion, resulting in myoglobinuria, elevated serum CK (usually > 5,000 in acute cases) and/or elevated AST in animals with normal liver function.

Local Muscle Strain

Muscle strain may be induced by inadequate warm-up, pre-existing lameness, exercise to the point of fatigue and insufficient training. The lumbar and gluteal muscles are frequently injured in jumpers, dressage and harness horses and the semimembranosus and semitendinosus muscles are more frequently damaged in working Quarter Horses performing abrupt turns and sliding stops (and may also occur secondary to intramuscular injections in this region). The gracilis muscle (adductor) can be torn through misadventure and creates swelling and pain in the medial thigh, and elevated serum CK.

Diagnosis: History, altered stride and reluctance to engage the hind quarters, and pain or heat on deep palpation of the muscles. CK and AST are usually only mildly elevated and thermography may assist with identification of affected muscle groups. Severe muscle trauma may be identifiable on ultrasound. In horses with chronic damage to the semimembranosus and semitendinosus, fibrotic myopathy may occur resulting in a characteristic gait.

Treatment: Rest and non-steroidal anti-inflammatory medication. Hand walking once the initial stiffness has dissipated. Rehabilitation: icing for acute injuries, therapeutic ultrasound, massage and stretching. Resume exercise gradually with appropriate warm-up. Check saddle for fit. If treating fibrotic myopathy surgical procedures can be tried (tenotomy of the tibial insertion of the semimembranosus tendon and/or transection (± excision) of the fibrotic area of muscle).

Exertional Rhabdomyolysis "Tying Up"

Exertional rhabdomyolysis represents a pathological description of a number of muscle diseases which have common clinical signs.

A useful way to classify tying-up is the following:

1. Sporadic Exertional Rhabdomyolysis

     - Occurs in healthy horses that have no previous history of muscle disease

     - Responds well to treatment

     - Environmental causes e.g. over-exertion (muscle strain), dietary imbalances of electrolytes, vitamin E and selenium, excessive grain in diet, viral infections.

2. Chronic Exertional Rhabdomyolysis

     - Occurs repeatedly in horses often following light exercise due to an intrinsic muscle defect

     - Recurs in spite of treatment

     - Two disorders are well described;

          a. Polysaccharide Storage Myopathy

          b. Recurrent Exertional Rhabdomyolysis

     - Idiopathic chronic exertional rhabdomyolysis also exists

Clinical signs:

     • Ranges from mild stiffness following exercise to recumbency, myoglobinuria and severe muscle damage. May have painful muscle cramps especially in the gluteal area.

     • Horses develop a short stiff stride, sweat profusely, and have an elevated respiratory rate. Reluctant to move, may posture to urinate +/- myoglobinuria.

     • Muscle pain usually persists for several hours.

     • Endurance horses may show other signs of exhaustion including a rapid heart rate, dehydration, hyperthermia, synchronous diaphragmatic flutter and collapse.

Diagnosis:

     • Decide if Sporadic or Chronic

     • History of muscle cramping and stiffness during or following exercise

     • Mild to marked elevations in serum CK, LDH and AST at rest or, if necessary perform an exercise challenge test (pre and 4 h post exercise serum CK, using 15-30 min of lunge work at a trot).

     • Serum vitamin E and whole blood selenium concentrations

     • Urinalysis and determination of renal excretion of electrolytes (Na, K, Phosphorus)

     • Genetic testing (or muscle biopsy if needed) to identify underlying cause

Treatment:

The objective of treatment is to relieve anxiety and muscle pain, correct fluid and acid base deficits and prevent renal compromise and further muscle damage.

1. Prevent further exertion of any kind

2. Oral and/or intravenous balanced polyionic fluids if dehydrated or myoglobinuric, Saline should be used in hyperkalemic animals

     a. Myoglobin can be nephrotoxic particularly if dehydrated or with concurrent NSAID therapy. Monitor BUN and serum creatinine if myoglobinuric. Continue fluid therapy until myoglobinuria resolved.

3. Monitor plasma electrolytes as severe muscle necrosis cause electrolyte imbalances.

4. Analgesia: lidocaine CRI, butorphanol, detomidine can be used. Care with NSAIDs especially if myoglobinuria or renal compromise present.

5. Acepromazine, is helpful in relieving anxiety and may increase muscle blood flow. Contraindicated in dehydrated horses.

6. Dantrolene sodium orally at 4 to 6 mg/kg every 8 hours to prevent further muscle damage.

7. Intravenous DMSO (< 10% solution) as an anti-inflammatory, free-radical scavenger and diuretic.

Management:

     - Rest with hand walking once the initial stiffness has abated.

     - Diet- good quality hay (grain supplementation only if necessary not exceeding 3 kg/day).

     - If chronic problem may benefit from an early return to a regular exercise schedule.

     - Resume training gradually, regular exercise, match the degree of exertion to the horse's fitness.

     - Recommendations for management of diet and training instituted based on which form of ER horse is most likely to have. If chronic;

     - A rigid, regular exercise schedule without days off

     - Good quality hay, a balanced vitamin and mineral supplement, and a minimum of grain (< 3kg). Extra caloric requirement above this should be given as corn oil or rice bran.

     - Reduction of stress and excitement is beneficial.

     - Endurance horses should be encouraged to drink electrolyte supplemented water during an endurance ride and monitored particularly closely during hot humid conditions.

Repair of skeletal muscle

Skeletal muscle shows remarkable ability to regenerate. Complete repair of muscle fibers without any residual scarring is dependant upon the degree of damage which occurs to the basement membrane surrounding each muscle fiber. Severe trauma or tearing of a muscle that results in destruction of the basement membrane usually results in the proliferation of connective tissue and scar formation. Rhabdomyolysis in foals and exertional myopathies in adult horses do not usually damage the basement membrane, thus complete repair of muscle tissue is possible within 4 - 8 weeks.

Specific Causes of Chronic Exertioal Rhabdomyolysis

1. Polysaccharide Storage Myopathy (PSSM):

     - A glycogen storage disorder characterized by the accumulation of glycogen and an abnormal polysaccharide in skeletal muscle. An autosomal dominant mutation in the glycogen synthase 1 gene found in ~ 80% of cases, resulting in unregulated glycogen synthesis. Reported most commonly in Quarter Horses, Draft horses and Warmbloods. Homozygotes and those with the concurrent malignant hyperthermia mutation are more severely affected. Clinical signs can occur in foals

Clinical signs:

     - Stiffness, fasciculations, sweating, firm painful muscles, and reluctance to move. The hindquarters are usually prominently affected.

     - Horses may park out or posture to urinate when ridden to relieve cramping.

     - Pawing and colic like episodes after exercise are also common.

     - Occasionally gait abnormalities and wasting (particularly the epaxial muscles) are seen.

     - Draft horses are commonly asymptomatic or may show weakness and muscle wasting.

     - There is no connection between PSSM and 'Shivers' in draft horses, the high prevalence of both conditions in these breeds led to a mistaken connection of the two.

Diagnosis:

     - Clinical signs

     - Elevated serum CK - may be persistent. Especially in light breeds.

     - Exercise challenge with 4-fold or more increase in serum CK 4 hrs after exercise.

     - Hair roots or whole blood for genetic testing for type 1 PSSM mutation in glycogen synthase 1 (GYS1) (http://www.cvm.umn.edu/umec/lab/home.html )

     - Muscle biopsy: abnormal (PAS-positive) polysaccharide inclusions in muscle biopsies that are resistant to digestion with amylase. Horses that have characteristic biopsy findings but lack GYS 1 mutation are classified as having Type 2 PSSM.

Homozygotes, and horses with concurrent RYR1 (MH) mutation appear to have a more severe phenotype than heterozygotes.

Treatment:

     - No cure. Treatment relies on appropriate diet and exercise changes

     - Manage acute cases as described above.

     - Daily access to pasture for at least 12 hours a day

     - Gradually increase the exercise level starting with lunging for a few minutes a day.

     - Diet: minimal grain, sweet feed or high carbohydrate rations (starch < 10% digestible energy per day)

     - Feed a fat supplement such as corn oil (maximum 2 cups/day/500kg horse) or rice bran (~ 4lb/day e.g. Natural Glow, EquiJewel) with a balanced mineral supplement or a high fat feed developed for tying-up such as Re-leve (see www.Re-leve.com).

     - For maximum effects BOTH dietary and exercise changes must be made.

2.Recurrent Exertional Rhabdomyolysis (RER):

Clinical signs:

     - Muscle stiffness ranging from mild to extremely severe, often preceded by excitement and stress.

     - Common in young nervous Thoroughbreds (5% prevalence), Standardbred and Arabian horses.

Diagnosis:

     - Intermittent increases in CK and AST with exercise (does not persist with rest) especially after a period of rest.

     - Muscle biopsies mostly normal with increased number of centrally located nuclei.

Etiology:

     - Autosomal dominant trait in Thoroughbreds

     - Numerous environmental factors contribute to the expression of the disease, including excitement, young age, gender, high grain diets and lameness.

     - Related to an underlying and but yet unidentified mutation affecting sk. muscle calcium regulation.

Table 1. Feeding recommendations for an average-sized horse (500 kg) with chronic exertional rhabdomyolysis at varying levels of exertion.

Treatment:

     - Alter the diet and environment to decrease excitability - turn-out, placing in barn, time of training etc

     - Feed <5 lbs of sweet feed /day if more calories are needed add fat (see above)

     - Exercise regularly with no days off.

     - Some horses need low doses of tranquilizers before exercise.

     - Drugs affecting Ca release from sarcoplasmic reticulum may be helpful (e.g. dantrolene, phenytoin)

     - Fillies may benefit from progesterone supplementation.

     - Ineffective drugs include sodium bicarbonate and dimethylglycine.

Table 2: Potential rations for a 500-kg horse with polysaccharide storage myopathy.

References

McKenzie EC, Valberg SJ and Pagan JD. Nutritional management of exertional rhabdomyolysis. In: Robinson NE, ed. Current Therapy in Equine Medicine 5. p. 727-734

McKenzie EC, Firshman AM. Optimal diet of horses with chronic exertional myopathies. Vet Clinics North America 2009 Apr;25(1):121-35, vii.